Bovine Digital Dermatitis (BDD) is an infectious inflammation of the skin near the claws of cattle defined as a circumscribed superficial ulceration of the skin along the coronary band, commonly on the plantar, interdigital ridge of the rear foot. The disease is associated with substantial pain and discomfort to the animal affected.
Digital dermatitis (DD) in general is a condition affecting a broad range of domesticated animals belonging to the botanical order of artiodactyla or even-toed ungulates, such as sheep, goats, pigs and cattle. While the present disclosure focuses on domesticated cattle, it is considered that the methods of the invention with minor modifications (to adjust mineral amounts according to the biology of the animal) will have the same beneficial effects on other domesticated, even-toed ungulates in need of treatment against digital dermatitis.
It is common to refer to domesticated, even-toed ungulates as claw-bearing animals, in contrast to uneven-toed ungulates, such as horses, which are often called hoofed animals. In the present disclosure, the common term of claw-bearing animals is used, with the understanding that in this disclosure it refers to domesticated, even-toed ungulates, in particular to sheep, goats, pigs, and cattle, more particular to sheep, goats, and cattle, and most particular to cattle.
Digital dermatitis is a significant economic problem for the farming industry both in terms of costs of treatment, as well as in terms of lowered economic value of the animal. Digital dermatitis, in particular, is a significant problem in the dairy industry, as animals infested with digital dermatitis in general have significantly lower production rates of milk, and often co-associated with lowered milk quality, thereby posing a significant economic problem for the dairy farmers.
The most common sites of digital dermatitis lesions (Dörte Döpfer, CanWest Veterinary Conference, 2009) is the palmar/plantar interdigital ridge of the foot—especially on the rear feet, but other sites include the skin of the interdigital cleft, where lesions can be found on the interdigital hyperplasias, the skin around the dewclaws, the heel, sometimes underrunning the sole, and the dorsal aspect of the coronary band, where the lesions may be associated with a vertical wall crack.
A scoring system for the severeness of lesions in cattle infected with digital dermatitis is in general use, ranging from M0 (negative), M1 (early), M2 (acute), M3 (severe), to M4, severe and including late chronic lesions.
It is generally recognized (N. Capion, Sund Klov, 2014, N. Capion et al. Open J. Vet. Med. 2013, 3, 192-198) that digital dermatitis is caused by bacteria of the family Treponema spp. Up to 10 different bacterial phylotypes of this family having been identified in digital dermatitis lesions, but the mechanism of infection remains unknown. E.g. Treponema were found in all cell samples of infested skin in a Danish investigation (N. Capion, 2013) comprising 100 cell samples from dairy cattle in the Stratum Spinosum skin layer, along with numerous other bacteria associated with domesticated cattle, however Treponema was completely absent in cell samples from the same cattle in any other location except in the digital dermatitis lesions sampled, indicating the close association of Treponema with digital dermatitis.
Numerous treatments for digital dermatitis have been suggested, as well as improvements in stall hygiene and daily care of the cattle, in particular adequate claw chipping or cutting. Currently, no single treatment of digital dermatitis has proven adequate without concomitant improvements in stall hygiene and daily care of the cattle. In general, the bacteriological infection levels in stalls are significant under modern production requirements and medication is in general insufficient to maintain a complement free from digital dermatitis infections.
Medicinal efforts have focused primarily on vaccination, antibiotics, and topical treatment with e.g. salicylic acid, chlortetracycline HCL, or other agents with known antibacterial (and/or antifungal) effects upon topical application.
EP 2724724 A1 describes the use of sprayable copper and zinc chelate formulations for the treatment and prevention of epithelial infections in sheep, goats, horses, and cattle, wherein the compositions comprise micronized copper and zinc chelates suspended in a liquid, wherein the total amount of copper and zinc chelate ranges from 5 to 50 percent by weight, and less than 5% (w/v) of the chelates are dissolved. By topically applying the solutions to digital dermatitis lesions in cattle in three-day intervals, healing was achieved at each wound site (characterized M1 and M2) with two treatments as observed by inspection on day 10.
A particularly suitable form of topical treatment for digital dermatitis in claw-bearing animals, in particular in cattle, is the use of bandages comprising salicylic acid, in particular salicylic acid powder, topically applied to the digital dermatitis lesion site of the claw of the animal.
Schulz and Capion (The Veterinary J. Vol 198, Issue 2, November 2013, pages 518-523, “Efficacy of salicylic acid in the treatment of digital dermatitis in dairy cattle”) report a study evaluating the efficacy of salicylic acid in the treatment of the digital dermatitis. A total of 201 DD lesions from 173 cows from four commercial dairy herds were evaluated at day 0 during routine hoof trimming and were allocated into two groups, namely, a control group given chlortetracycline spray, and a treatment group given 10 g of salicylic acid powder applied topically within a bandage. Pain, lesion size and clinical appearance (scored M0 to M4) were evaluated on days 3, 14 and 34 post-treatment. A change to M0 was defined as healing, while changes of M2 or M4 to M1 or M3 were classified as clinical improvements. Healing rates did not differ significantly between treatment groups at days 3 and 14. By day 34 the healing rate was fivefold better (P=0.01) for the treatment vs. the control group, with healing rates of 13.6% and 3.1%, respectively. By day 3, the rate of improvement was 2.5-fold better (P=0.02) for the controls. By day 34 the overall positive effect (i.e. healing and improvement) was 1.75-fold better (P=0.05) for the treatment group. Lesions from the control group were 2.2 times more likely (P=0.09) to have a pain score equal to 2 by day 14. The proportion of lesions getting smaller by days 14 and 34 was 2.5 times higher (P<0.08) for the treatment vs. the control group.
In the context of the present disclosure, salicylic acid bandages refer to any bandage for application to a digital dermatitis lesion site comprising sufficient salicylic acid, preferably as a powder, to effect a curing of the digital dermatitis lesion with an efficacy not worse than complete healing of the lesion in 30 days. Preferably, the amount of salicylic acid in the bandage shall be sufficient to achieve complete healing of the lesion in 20 days, more preferably in 15 days, even more preferably in 10 days, even more preferably in not more than 7 days, even more preferably in not more than 5 days, and most preferably in not more than 3 days. In the studies reported herein, bandages comprising sufficient salicylic acid powder to effect complete healing of a digital dermatitis lesion in a cow in usually two days were used in accordance with current Danish veterinary standards, with all lesions completely treated in 10 days or less.
It has been suggested that an improved clinical outcome can be achieved by supplying adequate amounts of trace minerals such as zinc or copper to cattle orally, e.g. in their diet as mineral supplements, e.g. Drendel et al. (The Pro. Anim. Sci, 21, p 217-224, 2005), Gomez et al. (J. Dairy Sci, 97, p 6211-6222), or N. Capion (Sund Klov, 2014). Concomitant treatment of digital dermatitis with topical antibacterial measures and zinc or copper mineral supplements have also been suggested.
Drendel et al. studied amino acid complexes of zinc, manganese and copper as a feed additive for dairy replacement heifers and the influence of these minerals in relation to claw disorders including digital dermatitis. The study was inconclusive regarding the overall effect of complex trace minerals on claw disorders. Gomez et al. studied the effect of trace minerals in a mineral premix comprising at least nine trace minerals, on the incidence of active digital dermatitis lesions in cattle and observed a statistically significant preventive effect of trace minerals on the prevention of digital dermatitis over a 45-day period.
With the present study, the inventor presents data indicating a beneficial effect on digital dermatitis in stabled cattle of orally supplying zinc and copper in the form of zinc and copper gluconates as feed additives for use in the prevention and cure of digital dermatitis. The tested procedure is applicable to the prevention and cure of digital dermatitis in all claw-bearing animals due to its simplicity and efficacy.
Zinc is a necessary component for the functioning of more than 300 different enzymes and plays a vital role in a large number of biological processes including skin healing and health. Zinc is a cofactor for the antioxidant enzyme, superoxide dismutase (SOD), and is involved in a number of enzymatic reactions in the carbohydrate and protein metabolism.
Zinc has a well-recognized importance as an immune-enhancing cofactor necessary for the regulation of T lymphocytes, CD4 cells, natural killer cells, and interleukin-2. In addition, it has been claimed that zinc possesses antiviral activity. Zinc is necessary for the maturation of sperm and normal fetal development. It is involved in sensory perception (taste, smell, and vision) and controls the release of stored vitamin A from the liver. In the endocrine system, zinc has been shown to regulate insulin activity and promote the conversion of the thyroid hormone thyroxine to triiodothyronine. It has been theorized that zinc improves claw integrity by speeding wound healing, increasing the rate of epithelial tissue repair and maintaining cellular integrity. Zinc is also required for the synthesis and maturation of keratin.
A particular problem with the administration of zinc to mammals is the low uptake of zinc in the digestive system. E.g., only 20% of added zinc is taken up by the digestive system when zinc is administered as pills of zinc oxide. The remaining zinc is excreted in the feces.
The present inventor has now surprisingly observed that feeding zinc, copper or, zinc and copper in the form of zinc gluconate and copper gluconate to stabled cattle already infected with digital dermatitis has a positive effect on the incidence level of digital dermatitis and on the general infectious level in the stabled cattle as measured as average cell count in milk.